Ticagrelor inverse agonist activity at the P2Y receptor is non-reversible versus its endogenous agonist adenosine 5´-diphosphate.

Background And Purpose: Ticagrelor is labelled as a reversible, direct-acting platelet P2Y receptor (P2Y R) antagonist that is indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As with many antiplatelet drugs, ticagrelor therapy increases bleeding risk in patients, which may require platelet transfusion in emergency situations. The aim of this study was to further examine the reversibility of ticagrelor at the P2Y R.

Ten tips for foundation doctors when making inpatient referrals to surgical specialties.

Making referrals to another specialty is an underemphasised skill in the undergraduate medical curriculum. As a result, many new foundation doctors find themselves ill-equipped to make effective referrals to other specialties as part of their day-to-day responsibilities. This can often be frustrating to the foundation doctor, the specialist and contribute to critical delays in patient care.

Platelet function following induced hypoglycaemia in type 2 diabetes.

Aim: Strict glycaemic control has been associated with an increased mortality rate in subjects with type 2 diabetes (T2DM). Here we examined platelet function immediately and 24hours following induced hypoglycaemia in people with type 2 diabetes compared to healthy age-matched controls.

Methods: Hyperinsulinaemic clamps reduced blood glucose to 2.

Loss of Cardioprotective Effects at the Locus as a Result of Gene-Smoking Interactions.

Background: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify.

Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease.

Background: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.

Objectives: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.

Comparison of exercise testing and CMR measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) Study.

Aims: To assess cardiovascular magnetic resonance (CMR) measured myocardial perfusion reserve (MPR) and exercise testing in asymptomatic patients with moderate-severe AS.

Methods And Results: Multi-centre, prospective, observational study, with blinded analysis of CMR data. Patients underwent adenosine stress CMR, symptom-limited exercise testing (ETT) and echocardiography and were followed up for 12-30 months.

Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC).

Objective/background: The management of aortic graft infection (AGI) is highly complex and in the absence of a universally accepted case definition and evidence-based guidelines, clinical approaches and outcomes vary widely. The objective was to define precise criteria for diagnosing AGI.

Methods: A process of expert review and consensus, involving formal collaboration between vascular surgeons, infection specialists, and radiologists from several English National Health Service hospital Trusts with large vascular services (Management of Aortic Graft Infection Collaboration [MAGIC]), produced the definition.

No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.

In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one.

Agreement between an online dietary assessment tool (myfood24) and an interviewer-administered 24-h dietary recall in British adolescents aged 11-18 years.

myfood24 Is an online 24-h dietary assessment tool developed for use among British adolescents and adults. Limited information is available regarding the validity of using new technology in assessing nutritional intake among adolescents. Thus, a relative validation of myfood24 against a face-to-face interviewer-administered 24-h multiple-pass recall (MPR) was conducted among seventy-five British adolescents aged 11-18 years.

Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen.

Unlabelled: Essentials Patients with cirrhosis have hemostatic changes, which may contribute to a risk of thrombosis. This in vitro study compares clot formation and structure between patients and healthy subjects. Clot formation is delayed in patients; ultimately, however, clot permeability is decreased.

Impact of sperm DNA chromatin in the clinic.

The paternal contribution to fertilization and embryogenesis is frequently overlooked as the spermatozoon is often considered to be a silent vessel whose only function is to safely deliver the paternal genome to the maternal oocyte. In this article, we hope to demonstrate that this perception is far from the truth. Typically, infertile men have been unable to conceive naturally (or through regular IVF), and therefore, a perturbation of the genetic integrity of sperm heads in infertile males has been under-considered.

Head injury from falls in children younger than 6 years of age.

Unlabelled: The risk of serious head injury (HI) from a fall in a young child is ill defined. The relationship between the object fallen from and prevalence of intracranial injury (ICI) or skull fracture is described.

Method: Cross-sectional study of HIs from falls in children (<6 years) admitted to UK hospitals, analysed according to the object fallen from and associated Glasgow Coma Score (GCS) or alert, voice, pain, unresponsive (AVPU) and CT scan results.

Development of a UK Online 24-h Dietary Assessment Tool: myfood24.

Assessment of diet in large epidemiological studies can be costly and time consuming. An automated dietary assessment system could potentially reduce researcher burden by automatically coding food records. myfood24 (Measure Your Food on One Day) an online 24-h dietary assessment tool (with the flexibility to be used for multiple 24 h-dietary recalls or as a food diary), has been developed for use in the UK population.

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.

Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.

Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22,193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium.

Cardiovascular imaging practice in Europe: a report from the European Association of Cardiovascular Imaging.

The need for cardiovascular imaging (CVI) is expected to increase over the coming years due to the changes in CV disease epidemiology and ageing of the population. However, reliable statistics on CVI practice in Europe are lacking. Establishing the current status of the use of CVI across Europe has become the first comprehensive project of the European Association of Cardiovascular Imaging and the European Society of Cardiology Taskforce on CVI.

Splenic Switch-off: A Tool to Assess Stress Adequacy in Adenosine Perfusion Cardiac MR Imaging.

Purpose: To investigate the pharmacology and potential clinical utility of splenic switch-off to identify understress in adenosine perfusion cardiac magnetic resonance (MR) imaging.

Materials And Methods: Splenic switch-off was assessed in perfusion cardiac MR examinations from 100 patients (mean age, 62 years [age range, 18-87 years]) by using three stress agents (adenosine, dobutamine, and regadenoson) in three different institutions, with appropriate ethical permissions. In addition, 100 negative adenosine images from the Clinical Evaluation of MR Imaging in Coronary Heart Disease (CE-MARC) trial (35 false and 65 true negative; mean age, 59 years [age range, 40-73 years]) were assessed to ascertain the clinical utility of the sign to detect likely pharmacologic understress.

Comparison of semi-automated methods to quantify infarct size and area at risk by cardiovascular magnetic resonance imaging at 1.5T and 3.0T field strengths.

Background: There is currently no gold standard technique for quantifying infarct size (IS) and ischaemic area-at-risk (AAR [oedema]) on late gadolinium enhancement imaging (LGE) and T2-weighted short tau inversion recovery imaging (T2w-STIR) respectively. This study aimed to compare the accuracy and reproducibility of IS and AAR quantification on LGE and T2w-STIR imaging using Otsu's Automated Technique (OAT) with currently used methods at 1.5T and 3.

Age- and sex-specific causal effects of adiposity on cardiovascular risk factors.

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals.

Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease.

Objective: Only a small fraction of coronary artery disease (CAD) heritability has been explained by common variants identified to date. Interactions between genes of importance to cardiovascular regulation may account for some of the missing heritability of CAD. This study aimed to investigate the role of gene-gene interactions in common variants in candidate cardiovascular genes in CAD.

Health-related quality of life after colorectal cancer in England: a patient-reported outcomes study of individuals 12 to 36 months after diagnosis.

Purpose: This population-level study was conducted to define the health-related quality of life (HRQL) of individuals living with and beyond colorectal cancer (CRC) and to identify factors associated with poor health outcomes.

Patients And Methods: All individuals diagnosed with CRC in England in 2010 and 2011 who were alive 12 to 36 months after diagnosis were sent a questionnaire. This included questions related to treatment, disease status, other long-term conditions (LTCs), generic HRQL (EuroQol-5D), and cancer-specific outcomes (Functional Assessment of Cancer Therapy and Social Difficulties Inventory items).

3.0T, time-resolved, 3D flow-sensitive MR in the thoracic aorta: Impact of k-t BLAST acceleration using 8- versus 32-channel coil arrays.

Purpose: To evaluate the performance of 4D flow MR in the thoracic aorta with 8- and 32-channel coil arrays using k-t BLAST and SENSE acceleration techniques and compare this to a conventional 2D SENSE approach.

Materials And Methods: Fifteen healthy subjects and eight patients underwent magnetic resonance imaging (MRI) at 3.0T using: 1) 2D SENSE phase contrast velocity mapping as the reference standard and 2) 4D-flow pulse sequences accelerated with SENSE and k-t BLAST, using both 8- and 32-channel coil arrays.